Cyclic compression loading alters osteoarthritis-related gene expression in three-dimensionally cultured human articular chondrocytes via a different mechanism than interleukin-1β induction

Abstract

Objectives

Mechanical and inflammatory stimuli are key factors in the pathophysiology of osteoarthritis (OA). However, the effects of mechanical stimulation on joint tissues and cells at the molecular level and the mechanisms of interaction after stimulation with inflammatory cytokines remains uninvestigated.

Methods

Three-dimensional cyclic compression loading (CCL) was applied to human articular chondrocytes, and the expression of OA-related genes was analyzed using reverse transcription quantitative real-time polymerase chain reaction. Additionally, the effects of CCL after the chondrocytes were stimulated with interleukin (IL)-1β were evaluated. A DNA microarray assay was used to compare changes in gene expression after chondrocytes were stimulated with IL-1β and CCL was applied, and to search for pathways that are affected by CCL.

Results

CCL of 40 kPa significantly upregulated the expression of IL-8, cyclooxygenase (COX)-2, nerve growth factor, matrix metalloproteinase (MMP)-1, and MMP-3. Transcription of IL-8, COX-2, and MMP-3 was synergistically promoted by CCL and IL-1β. The top 10 pathways enriched in the Kyoto Encyclopedia of Genes and Genomes enrichment analysis of differentially expressed genes were not common in either group, except for the “cytokine-cytokine receptor interaction”. The “tumor necrosis factor signaling pathway” and the “nuclear factor-kappa B signaling pathway” in the IL-1β group and “cell cycle” and the “Hippo signaling pathway” in the CCL group were included.

Conclusions

Comprehensive gene expression analysis revealed that CCL-induced changes in gene expression were different to those induced by stimulation with IL-1β. Our results provide new insights into the involvement of mechanical stimulation in the pathogenesis of OA.